Experimental and clinical observations have supported the concept that the hypothalamus plays a key role in the regulation of adenohypophysial corticotropic cells secretory functions. Over 25 years ago, Guillemin, Rosenberg and Saffran and Schally independently demonstrated the presence of factors in hypothalamus which would increase the rate of ACTH secretion by the pituitary gland incubated in vitro or maintained in an organ culture. None of the secretagogs characterized to date meets the criteria expected of a physiologic corticotropin releasing factor, CRF. Accordingly the purification of a large CRF has been pursued. Starting material for the purification was an early side fraction of the 490,000 ovine hypothalamic fragments originally extracted in the Laboratory for Neuroendocrinology at The Salk Institute, as described in Burgus et al. Hypothalamus and Endocrine Functions (F. Labrie et al. eds.) Plenum, New York, 1976, p. 355. None of the earlier attempts at purification were felt to have obtained this large molecular weight CRF in a purity of greater than about 1%.
Sauvagine is a 40-residue, amidated generally similar peptide which was isolated from the skin of the South American frog Phyllomedusa sauvagei, was characterized by Erspamer et al. and was described in Regulatory Peptides, Vol. 2 (1981), pp. 1-13. Sauvagine has the formula:
pGlu-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Ser-Leu-Glu-Leu-Leu-Arg-Lys-Met-Ile-Gl u-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-Ala-Asn-Asn-Arg-Leu-Leu-Leu-A sp-Thr-Ile-NH.sub.2. PA0 H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-L eu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu- Leu-Asp-Ile-Ala-NH.sub.2. PA0 Z-R.sub.1 -Pro-Pro-Ile-Ser-R.sub.8 -Asp-Leu-R.sub.11 -R.sub.12 -R.sub.13 -Leu-Leu-Arg-R.sub.17 -R.sub.18 -R.sub.19 -Glu-R.sub.21 -R.sub.22 -Lys-R.sub.24 -R.sub.25 -R.sub.26 -R.sub.27 -R.sub.28 -Gln-Gln-Ala-R.sub.32 -R.sub.33 -Asn-Arg-R.sub.36 -Leu-Leu-Asp-R.sub.40 -R.sub.41 -NH.sub.2 PA0 Z-R.sub.1 -Pro-Pro-Ile-Ser-R.sub.8 -Asp-Leu-R.sub.11 -R.sub.12 -R.sub.13 -Leu-Leu-Arg-R.sub.17 -R.sub.18 -R.sub.19 -Glu-R.sub.21 -R.sub.22 -Lys-R.sub.24 -R.sub.25 -R.sub.26 -R.sub.27 -R.sub.28 -Gln-Gln-Ala-R.sub.32 -R.sub.33 -Asn-Arg-R.sub.36 -Leu-Leu-Asp-R.sub.40 -R.sub.41 -NH.sub.2 PA0 X.sup.1 -R.sub.1 -Pro-Pro-Ile-Ser(X.sup.2)-R.sub.8 -Asp(X.sup.5)-Leu-R.sub.11 (X.sup.2)-R.sub.12 -R.sub.13 -Leu-Leu-Arg(X.sup.3)-R.sub.17 -R.sub.18 -R.sub.19 -Glu(X.sup.5)-R.sub.21 -R.sub.22 -Lys(X.sup.6)-R.sub.24 -R.sub.25 (X.sup.5)-R.sub.26 -R.sub.27 -R.sub.28 -Gln(X.sup.4)-Gln(X.sup.4)-Ala-R.sub.32 -R.sub.33 -Asn(X.sup.4)-Arg(X.sup.3)-R.sub.36 -Leu-Leu-Asp(X.sup.5)-R.sub.40 -R.sub.41 -X.sup.7 PA0 --O--CH.sub.2 -benzyl-polyamide resin support, PA0 --NH--benzhydrylamine (BHA) resin support, and PA0 --NH--paramethylbenzhydrylamine (MBHA) resin support.
Sauvagine has been reported to have biological activity in lowering blood pressure in mammals and in stimulating the secretion of ACTH and .beta.-endorphin.